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1.
Proc Natl Acad Sci U S A ; 121(6): e2312861121, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38285939

ABSTRACT

The N6-methyladenosine (m6A) modification of RNA is an emerging epigenetic regulatory mechanism that has been shown to participate in various pathophysiological processes. However, its involvement in modulating neuropathic pain is still poorly understood. In this study, we elucidate a functional role of the m6A demethylase alkylation repair homolog 5 (ALKBH5) in modulating trigeminal-mediated neuropathic pain. Peripheral nerve injury selectively upregulated the expression level of ALKBH5 in the injured trigeminal ganglion (TG) of rats. Blocking this upregulation in injured TGs alleviated trigeminal neuropathic pain, while mimicking the upregulation of ALKBH5 in intact TG neurons sufficiently induced pain-related behaviors. Mechanistically, histone deacetylase 11 downregulation induced by nerve injury increases histone H3 lysine 27 acetylation (H3K27ac), facilitating the binding of the transcription factor forkhead box protein D3 (FOXD3) to the Alkbh5 promoter and promoting Alkbh5 transcription. The increased ALKBH5 erases m6A sites in Htr3a messenger RNA (mRNA), resulting in an inability of YT521-B homology domain 2 (YTHDF2) to bind to Htr3a mRNA, thus causing an increase in 5-HT3A protein expression and 5-HT3 channel currents. Conversely, blocking the increased expression of ALKBH5 in the injured TG destabilizes nerve injury-induced 5-HT3A upregulation and reverses mechanical allodynia, and the effect can be blocked by 5-HT3A knockdown. Together, FOXD3-mediated transactivation of ALKBH5 promotes neuropathic pain through m6A-dependent stabilization of Htr3a mRNA in TG neurons. This mechanistic understanding may advance the discovery of new therapeutic targets for neuropathic pain management.


Subject(s)
Neuralgia , Trigeminal Neuralgia , Animals , Rats , AlkB Homolog 5, RNA Demethylase/genetics , AlkB Homolog 5, RNA Demethylase/metabolism , Neuralgia/genetics , Neuralgia/metabolism , RNA, Messenger/metabolism , Sensory Receptor Cells/metabolism , Transcription Factors/metabolism , Transcriptional Activation/genetics , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Receptors, Serotonin, 5-HT3/genetics
2.
Proc Natl Acad Sci U S A ; 121(5): e2320237121, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38252821

ABSTRACT

Dynamic 3D covalent organic frameworks (COFs) have shown concerted structural transformation and adaptive gas adsorption due to the conformational diversity of organic linkers. However, the isolation and observation of COF rotamers constitute undergoing challenges due to their comparable free energy and subtle rotational energy barrier. Here, we report the atomic-level observation and structural evolution of COF rotamers by cryo-3D electron diffraction and synchrotron powder X-ray diffraction. Specifically, we optimize the crystallinity and morphology of COF-320 to manifest its coherent dynamic responses upon adaptive inclusion of guest molecules. We observe a significant crystal expansion of 29 vol% upon hydration and a giant swelling with volume change up to 78 vol% upon solvation. We record the structural evolution from a non-porous contracted phase to two narrow-pore intermediate phases and the fully opened expanded phase using n-butane as a stabilizing probe at ambient conditions. We uncover the rotational freedom of biphenylene giving rise to significant conformational changes on the diimine motifs from synclinal to syn-periplanar and anticlinal rotamers. We illustrate the 10-fold increment of pore volumes and 100% enhancement of methane uptake capacity of COF-320 at 100 bar and 298 K. The present findings shed light on the design of smarter organic porous materials to maximize host-guest interaction and boost gas uptake capacity through progressive structural transformation.

3.
Biophys J ; 123(8): 931-939, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38454599

ABSTRACT

Guanosine monophosphate (GMP) is a nucleotide that can self-assemble in aqueous solution under certain conditions. An understanding of the process at the molecular level is an essential step to comprehend the involvement of DNA substructures in transcription and replication, as well as their relationship to genetic diseases such as cancer. We present the temperature-dependent terahertz (1.5-12 THz, 50-400 cm-1) absorptivity spectra of aqueous Na2 GMP solution in comparison with the aqueous solutions of other RNA nucleotides. Distinct absorption features were observed in the spectrum of GMP, which we attribute to the intramolecular modes of the self-assemblies (i.e., G-complexes) that, at 1 M, start to form at 313 K and below. Changes in broad-band features of the terahertz spectrum were also observed, which we associate with the release of hydration water in the temperature-dependent formation of guanine quadruplexes. Using a state-of-the-art THz calorimetry approach correlating spectroscopic to thermodynamic changes, we propose a molecular mechanism of hydrophilic hydration driving GMP self-assembly as a function of temperature. The free energy contribution of hydrophilic hydration is shown as a decisive factor in guanine-quadruplex formation. Our findings spotlight the role of hydration in the formation of macromolecular structures and suggest the potential of hydration tuning for regulating DNA transcription and replication.


Subject(s)
G-Quadruplexes , Guanosine Monophosphate , Guanosine Monophosphate/chemistry , Water/chemistry , Nucleotides , DNA/chemistry
4.
J Am Chem Soc ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602012

ABSTRACT

Zeolitic imidazolate frameworks (ZIFs) hold great promise in carbon capture, owing to their structural designability and functional porosity. However, intrinsic linker dynamics limit their pressure-swing adsorption application to biogas upgrading and methane purification. Recently, a functionality-locking strategy has shown feasibility in suppressing such dynamics. Still, a trade-off between structural rigidity and uptake capacity remains a key challenge for optimizing their high-pressure CO2/CH4 separation performance. Here, we report a sequential structural locking (SSL) strategy for enhancing the CO2 capture capacity and CH4 purification productivity in dynamic ZIFs (dynaZIFs). Specifically, we isolated multiple functionality-locked phases, ZIF-78-lt, -ht1, and -ht2, by activation at 50, 160, and 210 °C, respectively. We observed multiple-level locking through gas adsorption and powder X-ray diffraction. We uncovered an SSL mechanism dominated by linker-linker π-π interactions that transit to C-H···O hydrogen bonds with binding energies increasing from -0.64 to -2.77 and -5.72 kcal mol-1, respectively, as evidenced by single-crystal X-ray diffraction and density functional theory calculations. Among them, ZIF-78-ht1 exhibits the highest CO2 capture capacity (up to 18.6 mmol g-1) and CH4 purification productivity (up to 7.6 mmol g-1) at 298 K and 30 bar. These findings provide molecular and energetic insights into leveraging framework flexibility through the SSL mechanism to optimize porous materials' separation performance.

5.
Article in English | MEDLINE | ID: mdl-38867675

ABSTRACT

Positioned at the head of the nephron, the renal corpuscle generates a plasma ultrafiltrate to initiate urine formation. Three major cell types within the renal corpuscle, the glomerular mesangial cells, podocytes, and glomerular capillary endothelial cells communicate via endocrine and paracrine signaling mechanisms to maintain structure and function of the glomerular capillary network and filtration barrier. Ca2+ signaling mediated by several distinct plasma membrane Ca2+ channels modulates the functions of all three cell types. The last two decades have witnessed pivotal advances in understanding of Ca2+ channel function and regulation in glomerular cells, particularly non-voltage gated Ca2+ channels, in health and renal disease. This review summarizes the current knowledge of the physiological and pathological impact of non-voltage gated Ca2+ channel signaling in glomerular capillary endothelium, mesangial cells and podocytes. The main focus is on transient receptor potential and store-operated Ca2+ channels, but ionotropic N-methyl-D-aspartate receptors and purinergic 2X receptors also are discussed. This update of Ca2+ channel functions in the renal corpuscle and their cellular signaling cascades is intended to inform development of therapeutic strategies targeting these channels to treat kidney diseases, particularly diabetic nephropathy.

6.
Anal Chem ; 96(12): 4987-4996, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38466896

ABSTRACT

Surfactants are considered as typical emerging pollutants, their extensive use of in disinfectants has hugely threatened the ecosystem and human health, particularly during the pandemic of coronavirus disease-19 (COVID-19), whereas the rapid discrimination of multiple surfactants in environments is still a great challenge. Herein, we designed a fluorescent sensor array based on luminescent metal-organic frameworks (UiO-66-NH2@Au NCs) for the specific discrimination of six surfactants (AOS, SDS, SDSO, MES, SDBS, and Tween-20). Wherein, UiO-66-NH2@Au NCs were fabricated by integrating UiO-66-NH2 (2-aminoterephthalic acid-anchored-MOFs based on zirconium ions) with gold nanoclusters (Au NCs), which exhibited a dual-emission features, showing good luminescence. Interestingly, due to the interactions of surfactants and UiO-66-NH2@Au NCs, the surfactants can differentially regulate the fluorescence property of UiO-66-NH2@Au NCs, producing diverse fluorescent "fingerprints", which were further identified by pattern recognition methods. The proposed fluorescence sensor array achieved 100% accuracy in identifying various surfactants and multicomponent mixtures, with the detection limit in the range of 0.0032 to 0.0315 mM for six pollutants, which was successfully employed in the discrimination of surfactants in real environmental waters. More importantly, our findings provided a new avenue in rapid detection of surfactants, rendering a promising technique for environmental monitoring against trace multicontaminants.

7.
Planta ; 259(6): 147, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714547

ABSTRACT

MAIN CONCLUSION: CsNAC086 was found to promote the expression of CsFLS, thus promoting the accumulation of flavonols in Camellia sinensis. Flavonols, the main flavonoids in tea plants, play an important role in the taste and quality of tea. In this study, a NAC TF gene CsNAC086 was isolated from tea plants and confirmed its regulatory role in the expression of flavonol synthase which is a key gene involved in the biosynthesis of flavonols in tea plant. Yeast transcription-activity assays showed that CsNAC086 has self-activation activity. The transcriptional activator domain of CsNAC086 is located in the non-conserved C-terminal region (positions 171-550), while the conserved NAC domain (positions 1-170) does not have self-activation activity. Silencing the CsNAC086 gene using antisense oligonucleotides significantly decreased the expression of CsFLS. As a result, the concentration of flavonols decreased significantly. In overexpressing CsNAC086 tobacco leaves, the expression of NtFLS was significantly increased. Compared with wild-type tobacco, the flavonols concentration increased. Yeast one-hybrid assays showed CsNAC086 did not directly regulate the gene expression of CsFLS. These findings indicate that CsNAC086 plays a role in regulating flavonols biosynthesis in tea plants, which has important implications for selecting and breeding of high-flavonols-concentration containing tea-plant cultivars.


Subject(s)
Camellia sinensis , Flavonols , Gene Expression Regulation, Plant , Nicotiana , Plant Proteins , Camellia sinensis/genetics , Camellia sinensis/metabolism , Flavonols/biosynthesis , Flavonols/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Nicotiana/genetics , Nicotiana/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Oxidoreductases/genetics , Oxidoreductases/metabolism , Plant Leaves/metabolism , Plant Leaves/genetics , Plants, Genetically Modified
8.
Opt Express ; 32(1): 79-91, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38175064

ABSTRACT

In non-Hermitian systems, enhancing sensitivity under exceptional point (EP) conditions offers an ideal solution for reconciling the trade-off between sensitivity and size constraints in sensing applications. However, practical application is limited by undesired sensitivity to external fluctuations, noise, and errors in signal amplification synchronization. This paper presents a precisely controlled EP tracking and detection system (EPTDS) that achieves long-term rapid tracking and locking near the EP by constructing a second-order non-Hermitian optical sensing unit, employing an optical power adaptive control method, and utilizing a combinatorial demodulation-based dual-loop cascaded control (CDCC) technique to selectively suppress traditional noise at different frequencies. The system locking time is 10 ms, and in room temperature conditions, the output frequency error over 1 hour is reduced by more than 30 times compared to before locking. To assess its sensing capabilities, the EPTDS undergoes testing in a rotational experiment based on the Sagnac effect, with the output bias instability based on Allan deviation measured at 0.036 °/h. This is the best result for EP-enhanced angular rate sensing that we are aware of that has been reported. The EPTDS method can be extended to various sensing fields, providing a new path for transitioning non-Hermitian sensing from the laboratory to practical applications.

9.
Europace ; 26(4)2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38584395

ABSTRACT

AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7 ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8 min, and fluoroscopy time was 13.1 ± 7.6 min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Pulmonary Veins/surgery , Treatment Outcome , Prospective Studies , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Catheters , Catheter Ablation/adverse effects , Catheter Ablation/methods , Magnetic Phenomena , Recurrence
10.
Pacing Clin Electrophysiol ; 47(2): 275-280, 2024 02.
Article in English | MEDLINE | ID: mdl-38059637

ABSTRACT

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is characterized by episodes of rapid tachycardia with sudden onset and sudden termination. PSVT treatment has evolved considerably over the past 30 years. Currently, radiofrequency catheter ablation is the first-line treatment. HYPOTHESIS: We conducted a randomized controlled trial to compare safety and effectiveness of PSVT ablation between the Jinjiang and Johnson (J&J) catheters in 57 patients in our hospital. METHODS AND RESULTS: Patients were randomly assigned to ablation procedures using either the Jinjiang system or the J&J Carto system. Follow-up was performed 3 days, 1, and 6 months after the procedure. Success rate, ablation time, frequency of ablation, and rates of complications and recurrence did not significantly differ between the groups. One Jinjiang group patient (3.6%) experienced arrhythmia recurrence during the 6-month follow-up. CONCLUSIONS: The Jinjiang catheter for radiofrequency ablation of PSVT is as safe and effective as the J&J catheter.


Subject(s)
Catheter Ablation , Tachycardia, Paroxysmal , Tachycardia, Supraventricular , Tachycardia, Ventricular , Humans , Tachycardia, Paroxysmal/surgery , Catheter Ablation/methods , Tachycardia, Ventricular/surgery
11.
J Chem Phys ; 160(21)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38828818

ABSTRACT

Here, we report the frequency-dependent spectrum of ice Ih in the range of 0.2-2 THz. We confirm the presence of a feature that blue-shifts from around 1.55-1.65 THz with a decreasing temperature from 260 to 160 K. There is also a change in the trend of the refractive index of ice corresponding to a dispersion, which is also around 1.6 THz. The features are reproduced in data acquired with three commercial terahertz time-domain spectrometers. Computer-simulated spectra assign the feature to lattice translations perpendicular to the 110 and 1̄10 planes of the ice Ih crystal. The feature's existence should be recognized in the terahertz measurements of frozen aqueous solution samples to avoid false interpretations.

12.
Sensors (Basel) ; 24(8)2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38676115

ABSTRACT

In traditional tunnel monitoring, the characteristic points of an object within a tunnel are measured to obtain information about the object. Considering the limitations of the traditional method in measuring the complex surface structure of tunnels, such as limited monitoring points, a long measurement period, and low precision, this study introduces an approach that uses three-dimensional (3D) laser scanning for monitoring tunnel cross-section deformation. Using this approach, the soft surrounding rock of a high-altitude ultralong tunnel was taken as the monitoring object. The test tunnel was first scanned using a 3D laser scanner, and the collected data were processed. The internal structural data of the tunnel were subsequently compared with its actual contour lines and the data of its primary branch and secondary lining on different dates. The results indicate that the arch roof of the tunnel tended to be stable within a certain time range when the positions of the primary branch and secondary lining were at different measuring points with different pile numbers. The deformation of the pile number on the left and right sides did not generally exceed 0.02 m, except at a few measuring points. A comparison between the actual cross section of the initial branch and that of the designed section showed that the actual elevation of the arch of the initial branch of the tunnel was greater than its designed elevation by no more than 0.3 m. Hence, through this study, a convenient and practical method is presented for monitoring deformation in complex curved tunnel structures.

13.
Sensors (Basel) ; 24(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38276391

ABSTRACT

In the research of robot systems, path planning and obstacle avoidance are important research directions, especially in unknown dynamic environments where flexibility and rapid decision makings are required. In this paper, a state attention network (SAN) was developed to extract features to represent the interaction between an intelligent robot and its obstacles. An auxiliary actor discriminator (AAD) was developed to calculate the probability of a collision. Goal-directed and gap-based navigation strategies were proposed to guide robotic exploration. The proposed policy was trained through simulated scenarios and updated by the Soft Actor-Critic (SAC) algorithm. The robot executed the action depending on the AAD output. Heuristic knowledge (HK) was developed to prevent blind exploration of the robot. Compared to other methods, adopting our approach in robot systems can help robots converge towards an optimal action strategy. Furthermore, it enables them to explore paths in unknown environments with fewer moving steps (showing a decrease of 33.9%) and achieve higher average rewards (showning an increase of 29.15%).

14.
Aesthet Surg J ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38452172

ABSTRACT

BACKGROUND: Direct-to-implant (DTI) breast reconstruction after mastectomy has gained increasing popularity. While concerns over ischemic complications related to tension on the mastectomy flap persist, newer techniques and technologies have enhanced safety of this technique. OBJECTIVES: To compare clinical and patient-reported outcomes of DTI and two-stage tissue expander (TE) reconstruction. METHODS: A prospective cohort design was utilized to compare the incidence of reconstructive failure among patients undergoing DTI and TE reconstruction via unadjusted bivariate and adjusted multivariable logistic regression analyses. Secondary clinical outcomes of interest included specific complications requiring intervention (infection, seroma, hematoma, mastectomy flap necrosis, incisional dehiscence, device exposure) and time to final drain removal. Patient-reported outcomes (PROs) via BREAST-Q were also compared. RESULTS: A total of 134 patients (257 breasts) underwent DTI reconstruction and 222 patients (405 breasts) received TEs. DTI patients were significantly younger with lower BMIs, less diabetes, hypertension, and smoking, and smaller breast sizes, and underwent more nipple-sparing mastectomies with prepectoral reconstructions. Rates of any complication (18% DTI vs 24% TE, p=0.047), reconstructive failure (5.1% vs 12%, p=0.004), and seroma (3.9% vs 11%, p<0.001) were significantly lower in the DTI cohort on unadjusted analyses; however, there were no significant differences in adjusted regressions. Patient-reported satisfaction with breasts, psychosocial well-being, and sexual well-being were more substantively improved with DTI reconstruction. CONCLUSIONS: Prepectoral DTI reconstruction is a viable option for post-mastectomy reconstruction in carefully selected patients, with no significant increase in reconstructive failure or other complications.

15.
Saudi Pharm J ; 32(7): 102124, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38933713

ABSTRACT

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

16.
Angew Chem Int Ed Engl ; 63(21): e202400625, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38556897

ABSTRACT

Single-metal atomic sites and vacancies can accelerate the transfer of photogenerated electrons and enhance photocatalytic performance in photocatalysis. In this study, a series of nickel hydroxide nanoboards (Ni(OH)x NBs) with different loadings of single-atomic Ru sites (w-SA-Ru/Ni(OH)x) were synthesized via a photoreduction strategy. In such catalysts, single-atomic Ru sites are anchored to the vacancies surrounding the pits. Notably, the SA-Ru/Ni(OH)x with 0.60 wt % Ru loading (0.60-SA-Ru/Ni(OH)x) exhibits the highest catalytic performance (27.6 mmol g-1 h-1) during the photocatalytic reduction of CO2 (CO2RR). Either superfluous (0.64 wt %, 18.9 mmol g-1 h-1; 3.35 wt %, 9.4 mmol-1 h-1) or scarce (0.06 wt %, 15.8 mmol g-1 h-1; 0.29 wt %, 21.95 mmol g-1 h-1; 0.58 wt %, 23.4 mmol g-1 h-1) of Ru sites have negative effect on its catalytic properties. Density functional theory (DFT) calculations combined with experimental results revealed that CO2 can be adsorbed in the pits; single-atomic Ru sites can help with the conversion of as-adsorbed CO2 and lower the energy of *COOH formation accelerating the reaction; the excessive single-atomic Ru sites occupy vacancies that retard the completion of CO2RR.

17.
J Biol Chem ; 298(6): 101990, 2022 06.
Article in English | MEDLINE | ID: mdl-35490782

ABSTRACT

Podocyte injury induced by hyperglycemia is the main cause of kidney dysfunction in diabetic nephropathy. However, the underlying mechanism is unclear. Store-operated Ca2+ entry (SOCE) regulates a diversity of cellular processes in a variety of cell types. Calpain, a Ca2+-dependent cysteine protease, was recently shown to be involved in podocyte injury. In the present study, we sought to determine whether increased SOCE contributed to high glucose (HG)-induced podocyte injury through activation of the calpain pathway. In cultured human podocytes, whole-cell patch clamp indicated the presence of functional store-operated Ca2+ channels, which are composed of Orai1 proteins and mediate SOCE. Western blots showed that HG treatment increased the protein abundance of Orai1 in a dose-dependent manner. Consistently, calcium imaging experiments revealed that SOCE was significantly enhanced in podocytes following HG treatment. Furthermore, HG treatment caused overt podocyte F-actin disorganization as well as a significant decrease in nephrin protein abundance, both of which are indications of podocyte injury. These podocyte injury responses were significantly blunted by both pharmacological inhibition of Orai1 using the small molecule inhibitor BTP2 or by genetic deletion of Orai1 using CRISPR-Cas9 lentivirus. Moreover, activation of SOCE by thapsigargin, an inhibitor of Ca2+ pump on the endoplasmic/sarcoplasmic reticulum membrane, significantly increased the activity of calpain, which was inhibited by BTP2. Finally, the calpain-1/calpain-2 inhibitor calpeptin significantly blunted the nephrin protein reduction induced by HG treatment. Taken together, our results suggest that enhanced signaling via an Orai1/SOCE/Calpain axis contributes to HG-induced podocyte injury.


Subject(s)
ORAI1 Protein , Podocytes , Calcium/metabolism , Calcium Channels/metabolism , Calcium Signaling/physiology , Calpain/genetics , Calpain/metabolism , Glucose/metabolism , Glucose/pharmacology , Humans , Neoplasm Proteins/metabolism , ORAI1 Protein/genetics , ORAI1 Protein/metabolism , Podocytes/metabolism , Stromal Interaction Molecule 1/genetics , Stromal Interaction Molecule 1/metabolism
18.
Am J Physiol Renal Physiol ; 324(5): F494-F504, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36995925

ABSTRACT

Hyperglycemia and increased activity of the renal angiotensin II (ANG II) system are two primary pathogenic stimuli for the onset and progression of podocyte injury in diabetic nephropathy. However, the underlying mechanisms are not fully understood. Store-operated Ca2+ entry (SOCE) is an important mechanism that helps maintain cell Ca2+ homeostasis in both excitable and nonexcitable cells. Our previous study demonstrated that high glucose (HG) enhanced podocyte SOCE (1). It is also known that ANG II activates SOCE by releasing endoplasmic reticulum Ca2+. However, the role of SOCE in stress-induced podocyte apoptosis and mitochondrial dysfunction remains unclear. The present study was aimed to determine whether enhanced SOCE mediated HG- and ANG II-induced podocyte apoptosis and mitochondrial damage. In kidneys of mice with diabetic nephropathy, the number of podocytes was significantly reduced. In cultured human podocytes, both HG and ANG II treatment induced podocyte apoptosis, which was significantly blunted by an SOCE inhibitor, BTP2. Seahorse analysis showed that podocyte oxidative phosphorylation in response to HG and ANG II was impaired. This impairment was significantly alleviated by BTP2. The SOCE inhibitor, but not a transient receptor potential cation channel subfamily C member 6 inhibitor, significantly blunted the damage of podocyte mitochondrial respiration induced by ANG II treatment. Furthermore, BTP2 reversed impaired mitochondrial membrane potential and ATP production and enhanced mitochondrial superoxide generation induced by HG treatment. Finally, BTP2 prevented the overwhelming Ca2+ uptake in HG-treated podocytes. Taken together, our results suggest that enhanced SOCE mediated HG- and ANG II-induced podocyte apoptosis and mitochondrial injury.NEW & NOTEWORTHY This study tested the hypothesis that overwhelming store-operated Ca2+ entry is a novel mechanism contributing to high glucose- and angiotensin II-induced podocyte apoptosis and mitochondrial injury.


Subject(s)
Diabetic Nephropathies , Podocytes , Mice , Humans , Animals , Diabetic Nephropathies/metabolism , Angiotensin II/toxicity , Angiotensin II/metabolism , Podocytes/metabolism , Apoptosis , Glucose/toxicity , Glucose/metabolism
19.
J Med Virol ; 95(5): e28821, 2023 05.
Article in English | MEDLINE | ID: mdl-37227081

ABSTRACT

Acquired immune deficiency syndrome (AIDS)-related diffuse large B cell lymphoma (AR-DLBCL) is a rare disease with a high risk of mortality. There is no specific prognostic model for patients with AR-DLBCL. A total of 100 patients diagnosed with AR-DLBCL were enrolled in our study. Clinical features and prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by univariate and multivariate analyses. Central nervous system (CNS) involvement, opportunistic infection (OI) at lymphoma diagnosis, and elevated lactate dehydrogenase (LDH) were selected to construct the OS model; CNS involvement, OI at lymphoma diagnosis, elevated LDH, and over four chemotherapy cycles were selected to construct the PFS model. The area under the curve and C-index of GZMU OS and PFS models were 0.786/0.712; 0.829/0.733, respectively. The models we constructed showed better risk stratification than International Prognostic Index (IPI), age-adjusted IPI, and National Comprehensive Cancer Network-IPI. Furthermore, in combined cohort, the Hosmer-Lemeshow test showed that the models were good fits (OS: p = 0.8244; PFS: p = 0.9968) and the decision curve analysis demonstrated a significantly better net benefit. The prognostic efficacy of the proposed models was validated independently and outperformed the currently available prognostic tools. These novel prognostic models will help to tackle a clinically relevant unmet need.


Subject(s)
Acquired Immunodeficiency Syndrome , Lymphoma, Large B-Cell, Diffuse , Opportunistic Infections , Humans , Prognosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Multivariate Analysis
20.
Opt Express ; 31(16): 26697-26723, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37710524

ABSTRACT

The underwater environment poses great challenges, which have a negative impact on the capture and processing of underwater images. However, currently underwater imaging systems cannot adapt to various underwater environments to guarantee image quality. To address this problem, this paper designs an efficient underwater image enhancement approach that gradually adjusts colors, increases contrast, and enhances details. Based on the red channel maximum attenuation prior, we initially adjust the blue and green channels and correct the red channel from the blue and green channels. Subsequently, the maximum and minimum brightness blocks are estimated in multiple channels to globally stretch the image, which also includes our improved guided noise reduction filtering. Finally, in order to amplify local details without affecting the naturalness of the results, we use a pyramid fusion model to fuse local details extracted from two methods, taking into account the detail restoration effect of the optical model. The enhanced underwater image through our method has rich colors without distortion, effectively improved contrast and details. The objective and subjective evaluations indicate that our approach surpasses the state-of-the-art methods currently. Furthermore, our approach is versatile and can be applied to diverse underwater scenes, which facilitates subsequent applications.

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